title: DACT2 is a candidate tumor suppressor and prognostic marker in esophageal squamous cell carcinoma.
abstract: In animals ranging from fish to mice, the function of DACT2 as a negative regulator of the TGF-β/Nodal signal pathway is conserved in evolution, indicating that it might play an important role in human cancer. In this study, we showed that tumors with higher DACT2 protein level were correlated with better differentiation and better survival rate in patients with esophageal squamous cell carcinoma. Restored expression of DACT2 significantly inhibited growth, migration, and invasion of ESCC cells in vitro, and reduced tumorigenicity in vivo. Furthermore, when DACT2 expression was restored, the activity of TGF-β/SMAD2/3 was suppressed via both proteasome and lysosomal degradation pathways, leading to F-actin rearrangement that might depend on the involvement of cofilin and ezrin-redixin-moesin (ERM) proteins. Taken together, we propose here that DACT2 serves as a prognostic marker that reduces tumor cell malignancy by suppressing TGF-β signaling and promotes actin rearrangement in ESCC.
authors.affiliation: Institute of Oncologic Pathology, Medical College of Shantou University, Guangdong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
authors.forename: Lian-Di
authors.initials: LD
authors.lastname: Liao
authors.forename: Yang-Min
authors.initials: YM
authors.lastname: Xie
authors.forename: Fa-Min
authors.initials: FM
authors.lastname: Zeng
authors.forename: Xia
authors.initials: X
authors.lastname: Ji
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Li
authors.forename: Meng-Xiao
authors.initials: MX
authors.lastname: Zhu
authors.forename: Cui-Xia
authors.initials: CX
authors.lastname: Yang
authors.lastname: Qing-Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Xiu-E
authors.initials: XE
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Ming-Zhou
authors.initials: MZ
authors.lastname: Guo
authors.forename: En-Min
authors.initials: EM
authors.lastname: Li
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Xu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D002453:Cell Cycle; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C478653:DACT2 protein, human; D009363:Neoplasm Proteins; D053773:Transforming Growth Factor beta1